A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury

Ma, Jeff; Lau, Chi-Keung; Obed, Aiman; Dada, Alexander; Doenecke, Axel; Fan, Sheung‐Tat; Tsui, Tung Yu

doi:10.1038/gt.2008.162

Cited by 19 publications

(14 citation statements)

References 32 publications

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“…Interestingly emerging evidence indicates that the HO system suppresses different inflammatory events including macrophage infiltration [54, 63, 111, 202, 214] and potentiate insulin sensitivity and glucose metabolism in obesity [40, 111, 113] in a similar way as PPAR γ [209–213]. Accordingly, cross-talk between PPAR γ and the HO system has been reported [215].…”

Section: The Role Of Ho System In Inflammation and Insulin Resistancementioning

confidence: 99%

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Ndisang

2010

Mediators of Inflammation

141

151

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Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-α), interleukin (IL-6), IL-1β and resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-κB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-κB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.

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Section: The Role Of Ho System In Inflammation and Insulin Resistancementioning

confidence: 99%

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Ndisang

2010

Mediators of Inflammation

141

151

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“…Candidate cytoprotective genes include various heat shock proteins (HSPs) [8], B-cell leukemia/lymphoma-2(bcl-2), nitric oxide synthase, interleukins 4 and 10 [9, 10], and transforming growth factor- β 1 (TGF- β 1 ) [11]. The well-characterized gene heme oxygenase-1 (HO-1, HSP-32) prevents ischemia reperfusion (I/R) injury [12–17], promotes allograft and xenograft survival [1, 18–24], and prevents vascular remodeling [25–27]. HO-1 maintains cellular redox status, preserves vascular patency, and inhibits inflammation and apoptosis [18, 28].…”

Section: Introductionmentioning

confidence: 99%

Gene Transfer of Heme Oxygenase-1 Using an Adeno-Associated Virus Serotype 6 Vector Prolongs Cardiac Allograft Survival

Evans

Navarro

Doki

et al. 2012

Journal of Transplantation

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Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effectively administer HO-1 into the heart prior to transplantation to improve long-term graft outcome. Methods. HO-1 was delivered to the donor heart using an adeno-associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial growth factor (VEGF) to enhance myocardial tropism and microvascular permeability. Survival of mouse cardiac allografts, fully or partially mismatched at the MHC, was determined with and without cyclosporine A. Intragraft cytokine gene expression was examined by PCR. Results. The use of AAV6 to deliver HO-1 to the donor heart, combined with immunosuppression, prolonged allograft survival by 55.3% when donor and recipient were completely mismatched at the MHC and by 94.6% if partially mismatched. The combination of gene therapy and immunosuppression was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b, e and f were induced in the heart at rejection. Conclusions. Pretreatment of cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival. HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in cardiac transplantation.

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“…electroporation, lipid-or liposomally mediated gene transfer). In contrast to viral vectors, these gene transfer techniques generally do not induce an immune response in the recipient although their application is limited due to their low efficiency in vivo [129,130].…”

Section: Pharmacological Manoeuvresmentioning

confidence: 99%

Organ Preservation: Current Concepts and New Strategies for the Next Decade

Guibert

Petrenko

Balaban

et al. 2011

Transfus Med Hemother

279

233

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Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.

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A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury

Cited by 19 publications

References 32 publications

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity

Gene Transfer of Heme Oxygenase-1 Using an Adeno-Associated Virus Serotype 6 Vector Prolongs Cardiac Allograft Survival

Organ Preservation: Current Concepts and New Strategies for the Next Decade

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